Glycopyrrolate has been known for many years as an effective antimuscarinic agent. It has been used in several indications and been delivered by a number of different routes. It is currently used as an injectable primed to reduce secretions during anaesthesia and also as an oral product for treating gastric ulcers. One of the first descriptions of its use in airway disease was in 1984 where it was demonstrated to have a significant effect upon bronchodilation. Since then a number of studies have confirmed its potential utility.
Schroeckenstein et al., J. Allergy Clin. Immunol., 1988; 82(1): 115–119, discloses the use of glycopyrrolate in an aerosol formulation for treating asthma. A single administration of the metered-dose glycopyrrolate aerosol achieved bronchodilation over a 12 hour period.
Leckie et al., Exp. Opin. Invest. Drugs, 2000; 9(1): 3–23, is a general review of therapies for chronic obstructive pulmonary disease (COPD). Glycopyrrolate is mentioned as a possible drug treatment. However, there is no reference to its level of activity or to the duration at which it exerts its therapeutic effect.
Skorodin, Arch Intern. Med, 1993; 153: 814–828, discloses the use of glycopyrrolate in an aerosol formulation for the treatment of asthma and COPD. It is stated that, in general, the quaternary ammonium anticholinergic compounds have a duration of action of 4 to 12 hours. A dose of between 0.2 to 1.0 mg of glycopyrrolate is recommended at 6 to 12 hour intervals.
Walker et al., Chest, 1987; 91(1): 49–51, also discloses the effect of inhaled glycopyrrolate as an asthma treatment. Again, the duration of effective treatment is shown to be up to 12 hours, although up to 8 hours appears to be maximal.
WO-A-97/39758 discloses pharmaceutical compositions for treating respiratory inflammation containing the antioxidant tyloxapol. Page 23 refers to the addition of glycopyrrolate as an additional component in solution. There is no reference to the duration of activity of the glycopyrrolate, and the proposed effective dose (200–1000 μg) is similar to that described in the prior art above.
With this background, it is surprising to find that no glycopyrrolate formulation has been developed or registered for the treatment of airway disease. There are a number of possible reasons for this, and may include fears concerning systemic exposure and the drug binding at muscarinic receptors other than in the airways. This could result in both central and peripheral side-effects in patient populations that are already disposed to these complications. Such complications could be cardiovascular, ocular, mucosal or a predisposition to dizziness or fainting.